Abstract

Bone disease in patients with phenylketonuria (PKU) is incompletely characterized. We therefore analyzed, in a cross-sectional study radius macroscopic bone architecture and forearm muscle size by peripheral quantitative computed tomography (pQCT) and muscle strength by hand dynamometry in a large cohort (n = 56) of adolescent and adult patients with PKU aged 26.0 ± 8.9 (range, 11.8–41.5) years. Data were compared with a reference population (n = 700) from the DONALD study using identical methodology. We observed a significant reduction of cortical thickness (z-score −1.01 ± 0.79), Strength–Strain Index (SSI) (z-score −0.81 ± 1.03), and total bone mineral density (BMD) of the distal radius (z-score −1.05 ± 1.00). Mean muscle cross-sectional area (z-score −0.98 ± 1.19) and muscle grip force (z-score −0.64 ± 1.26) were also significantly reduced, indicating an impaired muscular system as part of the clinical phenotype of PKU. SSI positively correlated (r = 0.53, P < 0.001) with the corresponding muscle cross-sectional area in the reference population; however, the regression line slope in PKU patients was less steep (P < 0.001), indicating that bone strength is not adequately adapted to muscle force. In conclusion, the radial bone in PKU patients is characterized by reduced bone strength in relation to muscular force, decreased cortical thickness, and impaired total BMD at the metaphyseal site. These alterations indicate a mixed bone defect in PKU, both of which are due to primary alterations of bone metabolism and to secondary alterations in response to neuromuscular abnormalities.

Notes

Acknowledgements

The authors thank Vassiliki Konstantopoulou and Ariane Kleiner for participation in recruitment of patients. We thank Friedrich Karl Trefz and Peter Burgard for critically reviewing the manuscript.

Details of funding

This study was supported by grants from the Dietmar Hopp Foundation and Milupa Nutricia GmbH Germany. The authors confirm independence from the sponsors; the content of the article was no influenced by the sponsors.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki, 1975, as revised in 2000. Informed consent was obtained from all patients.